N 1-methylnicotinamide Is a Signalling Molecule Produced in Skeletal Muscle Coordinating Energy Metabolism

Sci Rep. 2018 Feb 14;8(1):3016. doi: 10.1038/s41598-018-21099-1.

Abstract

Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Caloric Restriction
  • Cells, Cultured
  • Energy Metabolism
  • Exercise / physiology*
  • Exercise Therapy
  • Humans
  • Lipid Metabolism
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology*
  • Muscle, Skeletal / physiology*
  • Niacinamide / analogs & derivatives*
  • Niacinamide / blood
  • Nicotinamide N-Methyltransferase / genetics*
  • Obesity / therapy*
  • Signal Transduction
  • Sweden
  • Transcriptome
  • Up-Regulation

Substances

  • Niacinamide
  • Nicotinamide N-Methyltransferase
  • N(1)-methylnicotinamide